title: Hypoxia induced multidrug resistance of laryngeal cancer cells via hypoxia-inducible factor-1α.
abstract: OBJECTIVE
  To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-1α (HIF- 1α).
  
  
  METHODS
  Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivity of the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining analysis, respectively. HIF-1α expression was blocked by RNA interference. The expression of HIF-1α gene was detected by real-time quantitative RT-PCR and Western blotting. The value of fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flow cytometry.
  
  
  RESULTS
  The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased (P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-1α expression.
  
  
  CONCLUSIONS
  HIF-1α could be considered as a key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China E-mail : zhouliang_lidawei@163.com.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.forename: Pin
authors.initials: P
authors.lastname: Dong
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Chen
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004317:Doxorubicin; D017239:Paclitaxel